Hypopharyngeal cancer is a severe malignancy with a poor prognosis and mortality rate. Neoadjuvant chemotherapy is one of the major methods of comprehensive treatment of head and neck squamous cell carcinoma and has been advocated in recent years with satisfactory results[4]. The evaluation of the efficacy of chemotherapy as early as possible has an important significance for the treatment and prognosis of patients. Various functional techniques, including positron emission tomography (PET)[5–9] or magnetic resonance imaging (MRI) diffusion-weighted imaging[10, 11] or dynamic contrast-enhanced MRI[9, 10], and CT perfusion[12, 13] were employed to evaluate the metabolism, hypoxia, cellularity, and perfusion of tumor. Nonetheless, some drawbacks, such as high cost, long scanning time, and poor resolution of small lesions, limit the clinical application of these methods. As new technology emerged in recent years, dual-source DECT imaging assesses the degree of tumor vascularization[14]. The applications of DECT in head and neck carcinoma (HNC) has increased, and several studies have shown the benefit of iodine characterization and virtual monoenergetic images for the detection and delineation of HNC[15, 16], differentiation between metastatic, inflammatory, and benign cervical lymph nodes[17–19], or assessment of cartilage invasion[20–22]. However, the role of DECT-derived quantitative imaging to predict oncological outcomes in hypopharyngeal squamous cell carcinoma has not yet been investigated.
The images obtained in this study were used to evaluate the efficacy based on the morphological changes of RECIST[23]; however, the internal tumor variation, such as liquefaction necrosis, is unable to make an effective assessment due to these limitations[24, 25]. The RECIST standard assesses the curative effect based on the change in the maximum tumor diameter, which might include tumor and necrotic areas, while the modified RECIST (mRECIST) standard uses “surviving tumors” as the evaluation criteria, excluding the affect of necrotics, recommended by 2010 EASL(European Association for the Study of the Liver) guidelines[26]. Dual-energy CT can obtain a series of derivative images, including iodine map, virtual non-enhanced image, single energy spectrum image, and nonlinear fusion image. Among these, the iodine-related attenuation measured in the iodine map quantificationally reflects the distribution and uptake of iodine in the lesion to reveal its blood supply condition. Moreover, the iodine-related attenuation is more reliable than the density value if the lesion is enhanced, for example the iodine-related attenuation is not affected by intratumoral hemorrhage. The content of iodine in the tissue can reflect its blood supply, and our results showed it might be a promising biological marker for evaluating the efficacy of chemotherapy. In this study, the patients with hypopharyngeal carcinoma with higher iodine-related attenuation were sensitive to induction chemotherapy. Zima et al.[27] reported that HNC with high perfusion were sensitive to radiotherapy and chemotherapy, which is consistent with the current conclusion. Thus, it could be postulated that the high perfusion state of tumor tissue can concentrate the local drug than the low perfusion state, thereby promoting the cell killing effect. The hypoperfusion state of tumor tissue might be considered as tumor ischemia and hypoxia, inducing the insensitivity to radiotherapy and chemotherapy.
Induction chemotherapy is one of the comprehensive treatment measures for advanced hypopharyngeal cancer. In 1991, the Laryngeal Cancer Group of American Veterans discovered the laryngeal function-sparing effects of chemotherapy and radiotherapy[28]. In 2003, the US RTOG 91 − 11 study confirmed that the laryngeal function-sparing rates of concurrent radiotherapy and chemotherapy (CRC), radiotherapy (RT), and induction chemotherapy + radiotherapy (IC + RT) were 84%, 66%, and 71%, respectively[29]. Currently, non-surgical treatments, including CRC, IC + RT, and RT combined with EGFR[30] are applied to preserve function in laryngeal and hypopharyngeal cancer patients. However, some patients not sensitive to chemotherapy should need surgery. So that evaluate the effectiveness of the chemotherapy and adjust the treatment plan in time are critical to the survival and prognosis of the patient. Currently, there is no effective method to predict the curative effect before induction chemotherapy. This study revealed that Dual-energy CT iodine map could be used to screen out the cases might have favorable effects before chemotherapy and avoid the inappropriate treatment plan for ineffective cases.
The RECIST morphological standard was as the reference to evaluate the tumor curative effect objectively. In order to eliminate the influence of the injection rate and dose of contrast agent among different individuals, a normalized iodine-related attenuation (NIRA) was applied in this study, which is the ratio of the iodine-related attenuation (IRA) in the ROI to the IRA in the carotid artery of the same layer. The present study showed that the NIRAs before chemotherapy was significantly related to the change of tumor diameter, including NIRAmean−A, NIRAmax−A, NIRAmean−P, and NIRAmax−P. For the different parametrics of NIRA, the NIRA at parenchymal phase had a larger area under the ROC curve and predicting specificity than the arterial phase, but the NIRAmean−A had a higher sensitivity. In addition to measuring the mean NIRA of maximum slice of lesion (NIRAmean), we also measured the NIRA of most enhanced region of lesion (NIRAmax) at the arterial and parenchymal phases which might avoid the influence of necrosis within the tumor. But the results showed that NIRAmean had a better predicting effect than NIRAmax, implied that NIRAmean might be better to reflect the global characteristic of tumor. The ROC curve reflects the correlation between the sensitivity and specificity of different NIRA parametrics, thereby rendering it as a comprehensive indicator of the test’s accuracy[31]. Other researches also confirmed that vascular iodine concentration reflects the efficacy of chemotherapy drugs within the tissue[32–36]. Yang et al.[37] revealed that patients with higher λHU values had a significantly low risk of progression and local recurrence, and DECT could easily identify CR patients and aid in choosing the appropriate treatment regimen for advanced laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). Bahig et al.[38] reported that maximum iodine concentration of the primary tumor and the high volume and iodine concentration standard deviation of involved lymph nodes predict the local regional recurrence in LHSCC. Therefore, DECT provides valuable information to evaluate the response of hypopharyngeal carcinoma which might be important for the clinical implementation of individualized treatment. In addition, Ge et al.[39] compared the radiation dose of DECT and conventional CT scan mode and did not find any significant difference in the mean radiation dose between DECT and the conventional CT scan, indicating that DECT did not cause additional radiation damage and was safe and suitable for efficacy evaluation.
Nevertheless, the present study has several limitations. The evaluation was only for short-term efficacy, and the reliability of the results for the long-term prognosis requires further verification with large sample data. Using dual-source CT iodine-related measurement to predict the effect of chemotherapy is a universal law based on correlation, and its accuracy and feasibility need to be assessed for individual cases. Moreover, the accuracy of iodine-related attenuation measurement is hindered by several factors.